Field of the Invention
The present invention relates to a composition for preventing or treating obesity, dyslipidemia, fatty liver or insulin resistance syndrome containing piperonal as an active ingredient.
Background of Technique
As abdominal obesity increases in modern people with the change in lifestyles, occurrence of metabolic syndromes including diabetes, hypertension, dyslipidemia, insulin resistance, etc. is increasing rapidly. These diseases increase the risk of incidence one another and are commonly related to the cause of metabolic changes, such as aging, stress and suppressed immune system. Obesity is considered unattractive and causes such chronic diseases as fatty liver, hypertension, diabetes, cardiovascular diseases, or the like. According to the 2007 Korea National Health and Nutrition Examination Survey recently reported by the Ministry of Health & Welfare, 31.7% of Korean adults turned out to be obese, meaning that 3 out of 10 Korean adults are exposed to obesity-related complications. The increase in overweight and obese population leads to increased prevalence of chronic diseases. The number of diabetic patients in Korea is expected to increase from 3,000,000 in 2007 to 5,450,000 in 2030, meaning that 10% of Koreans will be diabetic patients. In 2005, deaths caused by diabetes in Korea were 35.5 per 100,000 people, 3-7 times more than those of Japan (5.9), England (7.5) or Germany (16.6). According to the Korea Institute for Health and Social Affairs, the socioeconomic loss caused by obesity and obesity-related complications in 2006 is estimated at 2.1 trillion won including medical cost and indirect cost such as loss of earning. Thus, in 2010, the Korean government has decided to reduce the obesity rate down to 20% in adults and to 15% in youth, and is exploring ways to accurately define and diagnose obesity and metabolic diseases.
At present, 1.7 billion people amounting to about 25% of the world population are overweight (BMI>25) and more than 300 million people including 120 million in the US, Europe and Japan are classified as obese (BMI>30). Among the OECD countries, the US has the highest obesity rate of 31% of population, followed by Mexico (24%), England (23%), Greece (22%), Australia (22%), New Zeeland (21%), Hungary (19%), Canada (14%), Spain (13%), Ireland (13%), Germany (13%), Portugal (13%), Finland (13%), Turkey (12%) and Belgium (12%). The number of obese people in China is 70 million and the body weight control-related market is expanding, estimated at about 10 billion yuan. Childhood obesity is also increasing rapidly worldwide, with 1 in 5 children being obese. As such, childhood obesity is becoming a serious social issue. Since childhood obesity is the main cause of the life style diseases including diabetes, hypertension, stroke, etc. with increased blood cholesterol and triglyceride level, 80% or more of obese children are likely to become obese adults. Further, since increased fat stimulates secretion of sex hormones and induces early adolescence, childhood obesity may cause growth problems. Also, it negatively affects blood circulation and nourishment.
Obesity drugs that are marketed inside and outside Korea include ‘Xenical’ (Roche Korea) with orlistat as main ingredient and approved by the FDA, ‘Reductil’ (Ilsung Pharmaceuticals) with sibutramine as main ingredient, ‘Exolise’ (Guju Pharma) with green tea catechol as main ingredient, or the like. Xenical, which reduces absorption of fat by inhibiting lipase, has the gastrointestinal-related side effects such as steatorrhea, gas generation and reduced absorption of oil-soluble vitamins. Reductil, which increases serotonin and noradrenaline levels in the sympathetic nervous system, has side effects such as headache, dry mouth, loss of appetite, insomnia, constipation, etc. Besides, a large number of anti-obesity drugs have been withdrawn from the market due to severe side effects. For example, aminophylline is reported to have various side effects in the nervous, circulatory and digestive systems despite its excellent effect of reducing body fat. Also, fenfluramine, dexfenfluramine, topiramate, ephedrine, etc. have been banned from being marketed as obesity drugs. As the synthetic drugs show limitations in side effects and in overcoming chronic diseases, foods and drugs derived from natural sources are drawing attentions.
Piperonal is named as heliotropine (heliotropin), dioxymethyleneprotocatechuic aldehyde, piperonyl aldehyde, 3,4-benzodioxole-5-carboxaldehyde, 1,3-benzodioxole-5-carboxaldehyde, 3,4-methylene dihydroxybenzaldehyde. Piperonal contained in Capparis spinosa Linne (Caper), Cinnamomum camphora (Camphor), Cucumis melo Linn, Galium verum var. asiaticum, Piper nigrum (Black Pepper), Polianthes tuberosa (Tuberose), Vaccinium colymbosum (American blueberry), Vanilla planifolia (Bourbon vanilla), Viola odorata (Apple leaf) is alkaloids compounds.
Piperonal has the molecular formula of C8H6O3 and the molecular weight of 150.13 g/mol, represented by the following chemical formula:

Piperonal has been registered in the food additives database of FDA (Food and Drug Administration) and KFDA (Korea Food and Drug Administration) as flavoring substance with edible substance. It has been also used for combination of spices based on cherry and vanilla, and ice cream and bakery products mainly. Piperonal has been reported to have cancer inhibitory effect in cancinogenesis animal model (Anto R J, George J, Babu K V, Rajasekharan K N, Kuttan R., Antimutagenic and anticarcinogenic activity of natural and synthetic curcuminoids. Mutat Res. September 13; 370(2):127-31 (1996)). It has been also reported that patients feel relief from anxiety as a result of stimulated sense of smell by piperonal through nasal cannula during MRI (magnetic resonance imaging) for cancer diagnosis (Redd W H, Manne S L, Peters B, Jacobsen P B, Schmidt H., Fragrance administration to reduce anxiety during MR imaging. J Magn Reson Imaging. July-August; 4(4):623-6, 1994).
Piperonal is known as an edible substance with a significant high safety. In other words, there was no toxicity although human took 10 g of piperonal (Von Oettingen, W. F., Nat Inst Health Bull. No. 190, 342 (1949)) and it is noteworthy that the reported LD50 of piperonal is more than 2,700 mg/kg (rats) (Jenner, P. M., et al., Food Cosmet Toxicol. 2, 327, (1964)). Furthermore, there were no abnormalities on blood, weight of major organs and histology in an experiment of intaking feed containing 1% piperonal to rats for 28 weeks (Hagan, E. C., et al., Fd Cosmet Toxicol. 5, 141 (1967)). There was no toxicity in an experiment of intaking feed containing 0.1% piperonal and 0.5% piperonal to rats for 2 years (FAO Nutr. Meet. Rep. Ser. No. 44A. WHO Fd. Add. 68, 33, 73, (1968)).
Throughout the specification, a number of publications and patent documents are referred to and cited. The disclosure of the cited publications and patent documents is incorporated herein by reference in its entirety to more clearly describe the state of the related art and the present disclosure.